US5247091A - Preparation of enamines in aqueous media - Google Patents
Preparation of enamines in aqueous media Download PDFInfo
- Publication number
- US5247091A US5247091A US07/921,791 US92179192A US5247091A US 5247091 A US5247091 A US 5247091A US 92179192 A US92179192 A US 92179192A US 5247091 A US5247091 A US 5247091A
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- US
- United States
- Prior art keywords
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- formula
- compound
- loweralkyl
- acid
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- Expired - Fee Related
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/08—Nitrogen atoms
- C07D219/10—Nitrogen atoms attached in position 9
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Definitions
- Enamines are generally prepared in non-aqueous media with removal of the formed water by azeotropic distillation with an aromatic solvent such as benzene, by the use of drying agents such as molecular sieves, and by the use of water scavengers such as titanium tetrachloride. While these methods provide enamines in good yields and of sufficient purity for subsequent conversions to products of commercial significance, the use and disposal of aromatic solvents, molecular sieves, and titanium halides present a health hazard and degrade the environment, and diminish the cost effectiveness of processes for the preparation of such compounds as intermediates for the synthesis of medicinal or other products of commerce. See, for example, L. W. Haynes and A. G. Cook in "Enamines--Synthesis, Structure, and Reactions," 2nd Edition, A. G. Cook, Editor, Marcel Dekker, Inc., New York, N.Y., 1988, pages 103 to 114, and Chapter 9.
- enamines of cycloalkanones and cycloalkandiones and anilines can be prepared in high yield and high purity in aqueous media under conditions commonly used to cleave enamines, thereby avoiding the health and environmental hazards associated with the water removal and drying methods, used previously, and improving the cost effectiveness of commercial processes employing enamines. See, for example, S. F. Dyke, "The Chemistry of Enamines," Cambridge University Press, London, England, 1973, pages 8 and 9.
- the present invention relates to a process for the synthesis of enamines of cycloalkanones and cycloalkandiones and anilines in aqueous medium. More particularly, the present invention relates to a process for the synthesis of enamines of formula 1 ##STR1## wherein R is CN, CO 2 H, or CO 2 R 1 wherein R 1 is loweralkyl; Y is CH 2 or C ⁇ O; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, NHCOR 2 wherein R 2 is loweralkyl, or a group of the formula NR 3 R 4 wherein R 3 and R 4 are independently hydrogen or loweralkyl; and n is 0, 1, or 2, which comprises condensing an aniline of formula 2 ##STR2## wherein R and X are as hereinbeforedefined with a cycloalkanone or -dione 3 ##STR3## wherein Y and n are as hereinbeforedefined in aqueous
- the preferred aqueous medium is water containing an acidic promoter.
- Cosolvents such as alkanols, e.g., ethanol, 2-propanol, 1,1-dimethylethanol, and the like, may be employed, however, to facilitate the condensation by dissolution of components 2 and 3.
- the condensation proceeds at a reasonable rate at temperatures from about -10° C. to about the reflux temperature of the reaction medium, the reaction temperature being dependent on the nature of the components 2 and 3. Lower temperatures are, for example, generally employed when component 3 wherein Y is C ⁇ O is used; higher temperatures when component 3 wherein Y is CH 2 is used.
- a condensation temperature of about 40° C. is preferred when a dione 3 wherein Y is C ⁇ O is used; a condensation temperature about the reflux temperature of the medium is preferred when an one 3 wherein Y is CH 2 is used.
- the condensation reaction of aniline 2 and cycloalkanone or -dione 3 is usually complete within about one hour when component 3 wherein Y is C ⁇ O is used; about 3 days when component 3 wherein Y is CH 2 is used. Longer reaction times are generally, however, not detrimental.
- aniline 2 and cycloalkanone or -dione 3 are usually employed in the condensation reaction.
- An excess (ca 10%) of aniline 2 may be used to further facilitate the reaction.
- an aniline 2 and a cycloalkanone or -dione 3 proceeds at a convenient rate to provide the desired enamine 1 in good yield and a high state of purity.
- an acid promoter such as a mineral acid or an organic acid is used.
- mineral acids there may be mentioned hydrohalic acids such as hydrochloric acid, hydrobromic acid, and hydriodic acid, nitric acid, sulfuric acid, and phosphoric acid.
- organic acids there may be mentioned carboxylic acids such as acetic acid and trifluoroacetic acid, and sulfonic acids such as benzenesulfonic acid, 4-methylbenzenesulfonic acid, methanesulfonic acid, and ethanesulfonic acid.
- carboxylic acids such as acetic acid and trifluoroacetic acid
- sulfonic acids such as benzenesulfonic acid, 4-methylbenzenesulfonic acid, methanesulfonic acid, and ethanesulfonic acid.
- Hydrochloric acid is the preferred mineral acid
- 4-methylbenzenesulfonic acid is the preferred organic acid.
- the intermediate enamines 1 provided by condensation of an aniline 2 with a cycloalkanone or -dione 3, the process of the present invention, are useful for the preparation of memory enhancing 9-amino-1,2,3,4-tetrahydroacridines 4 ##STR4## wherein X, Y, and n are as hereinbeforedescribed by conventional cyclization methods.
- Cuprous chloride is generally employed as the condensation catalyst. See, for example, U.S. Pat. No. 4,631,286 issued Dec. 23, 1986 to G. M. Shutske and F. A. Pierrat for the cyclization of related enamines and W. K. Summers, et al., New England Journal of Medicine, 315, 1241 (1986) for a discussion of the cognition activating properties of the ultimate product.
- the reduction of 4 to 5 may also be carried out by catalytic hydrogenation (e.g., by hydrogen in glacial acetic acid, ethanol, or 2-propanol at a hydrogen pressure of about 10 to about 350 psig and a temperature of 20° to 80° C. in the presence of palladium, platinum, rhodium, or ruthenium, free or supported on, for example, carbon or strontium carbonate).
- catalytic hydrogenation e.g., by hydrogen in glacial acetic acid, ethanol, or 2-propanol at a hydrogen pressure of about 10 to about 350 psig and a temperature of 20° to 80° C. in the presence of palladium, platinum, rhodium, or ruthenium, free or supported on, for example, carbon or strontium carbonate.
- the condensation of an aniline 2 and cycloalkanone or -dione 3 may be carried out in a one-pot reaction sequence without isolation of the intermediate enamine 1 to provide a 9-amino-1,2,3,4-tetrahydroacridine 4 in good yield and pure state.
- treatment of 2-aminobenzontirile 2 wherein R is CN and X is hydrogen with cyclohexanone 3 wherein Y is CH 2 and n is 1 in the presence of concentrated hydrochloric acid and cuprous chloride at the reflux temperature of the medium affords pure 9-amino-1,2,3,4-tetrahydroacridine 4 wherein X is hydrogen, Y is CH 2 , and n is 1 in high yield.
- the ultimate 9-amino-1,2,3,4-tetrahydroacridines 4 are, as hereinbeforementioned, obtained either directly or via the intermediate enamines 1 of the present invention when 2-aminobenzonitriles 2 wherein R is CN are employed as one of the reactants.
- 2-aminobenzoic acids 2 (or esters thereof) wherein R is CO 2 H or CO 2 R 1 wherein R 1 is loweralkyl are employed, enamines 1 wherein R is CO 2 H or CO 2 loweralkyl are obtained.
- Enamines 1 wherein R is CO 2 H or CO 2 loweralkyl may be converted to enamines 1 wherein R is CN or cyclized to 9-oxoacridines 6 ##STR6## wherein X, Y, and n are as hereinbeforedescribed, which, in turn, may be converted to 9-aminoacridines 4 by methods known in the art. See, for example, A. Oshirk and E. B. Pederson, Acta Chemica Scandinavica B, 33, 313 (1979).
- the enamine intermediates of the present invention are recovered by ordinary separation techniques, usually filtration.
- the starting materials for the enamine and acridine synthesis of the present invention i.e., the 2-aminobenzonitriles 2 and 2-aminobenzoic acids 2 (and esters thereof) and cycloalkanones and -diones 3 are commercially available or preparable by conventional methods.
- alkyl refers to a straight or branched chain hydrocarbon radical containing no unsaturation and having 1 to 10 carbon atoms such as methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-pentyl, 2-pentyl, 3-hexyl, 4-heptyl, 2-octyl, 3-nonyl, 4-decyl and the like;
- alkoxy refers to a monovalent substituent which consists of an alkyl group linked through an ether oxygen and having its free valence bond from the ether oxygen such as methoxy, ethoxy, propoxy, butoxy, 1,1-dimethylethoxy, pentoxy, 3-methylpentoxy, 2-ethylpentoxy, 2-methyloctoxy, octoxy, decoxy, and the like;
- halogen refers to a member of the family fluorine, chlorine, bromine or i
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/921,791 US5247091A (en) | 1992-07-30 | 1992-07-30 | Preparation of enamines in aqueous media |
MX9304594A MX9304594A (es) | 1992-07-30 | 1993-07-19 | Procedimiento para preparar enaminas en medios acuosos. |
TW082105784A TW226363B (xx) | 1992-07-30 | 1993-07-21 | |
EP93111751A EP0581194A1 (en) | 1992-07-30 | 1993-07-22 | A process for the preparation of enamines in aqueous media |
NZ248266A NZ248266A (en) | 1992-07-30 | 1993-07-28 | Preparation of intermediate enamines useful for the subsequent preparation of 9-amino-1,2,3,4-tetrahydroacridines and analogues thereof |
NZ280133A NZ280133A (en) | 1992-07-30 | 1993-07-28 | Preparation of 9-amino-1,2,3,4-tetoahydroacridines |
FI933384A FI933384A (fi) | 1992-07-30 | 1993-07-28 | Foerfarande foer framstaellning av enaminer i ett vattanhaltigt medium |
IL106530A IL106530A0 (en) | 1992-07-30 | 1993-07-29 | Preparation of enamines in aqueous media |
PL93299871A PL299871A1 (en) | 1992-07-30 | 1993-07-29 | Method of obtainingenamines in aqueous environment |
KR1019930014501A KR940005548A (ko) | 1992-07-30 | 1993-07-29 | 수성 매질 속에서의 엔아민의 제조방법 |
CA002101568A CA2101568A1 (en) | 1992-07-30 | 1993-07-29 | Preparation of enamines in aqueous media |
AU44245/93A AU674323B2 (en) | 1992-07-30 | 1993-07-29 | Preparation of enamines in aqueous media |
HU9302214A HUT65497A (en) | 1992-07-30 | 1993-07-29 | A process for the preparation of enamines in aqueous media |
NO932732A NO179581C (no) | 1992-07-30 | 1993-07-29 | Fremgangsmåte for fremstilling av enaminer i vandige media |
JP5186544A JPH0820577A (ja) | 1992-07-30 | 1993-07-29 | 水性媒質中でエナミンを製造する方法 |
CN93109307A CN1085208A (zh) | 1992-07-30 | 1993-07-29 | 在水相介质中的烯胺制备方法 |
NO960854A NO960854D0 (no) | 1992-07-30 | 1996-03-01 | Fremgangsmåte for fremstilling av 9-amino-1,2,3,4-tetrahydroakridiner |
FI964670A FI964670A (fi) | 1992-07-30 | 1996-11-22 | Menetelmä 9-amino-1,2,3,4-tetrahydorakridiinin valmistamiseksi |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/921,791 US5247091A (en) | 1992-07-30 | 1992-07-30 | Preparation of enamines in aqueous media |
Publications (1)
Publication Number | Publication Date |
---|---|
US5247091A true US5247091A (en) | 1993-09-21 |
Family
ID=25445981
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US07/921,791 Expired - Fee Related US5247091A (en) | 1992-07-30 | 1992-07-30 | Preparation of enamines in aqueous media |
Country Status (15)
Country | Link |
---|---|
US (1) | US5247091A (xx) |
EP (1) | EP0581194A1 (xx) |
JP (1) | JPH0820577A (xx) |
KR (1) | KR940005548A (xx) |
CN (1) | CN1085208A (xx) |
AU (1) | AU674323B2 (xx) |
CA (1) | CA2101568A1 (xx) |
FI (1) | FI933384A (xx) |
HU (1) | HUT65497A (xx) |
IL (1) | IL106530A0 (xx) |
MX (1) | MX9304594A (xx) |
NO (1) | NO179581C (xx) |
NZ (1) | NZ248266A (xx) |
PL (1) | PL299871A1 (xx) |
TW (1) | TW226363B (xx) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994021614A1 (en) * | 1993-03-24 | 1994-09-29 | Merck & Co., Inc. | SUBSTITUTED 3-PHENANTHRIDINONE DERIVATIVES AS 5α-REDUCTASE INHIBITORS |
WO2012074860A1 (en) | 2010-12-03 | 2012-06-07 | Dow Agrosciences Llc | Processes for the preparation of enamines |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4631286A (en) * | 1984-10-25 | 1986-12-23 | Hoechst-Roussel Pharmaceuticals Inc. | 9-amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE791474A (fr) * | 1971-11-25 | 1973-03-16 | Yamanouchi Pharma Co Ltd | Procede de preparation de derives d'acides cycloalcoylaminoarylcarboxyliques |
DE3582995D1 (de) * | 1984-10-25 | 1991-07-04 | Hoechst Roussel Pharma | 9-amino-1,2,3,4-tetrahydroacridin-1-ol und verwandte verbindungen, verfahren zu ihrer herstellung und verwendung als arzneimittel. |
US4754050A (en) * | 1984-10-25 | 1988-06-28 | Hoechst-Roussel Pharmaceuticals, Inc. | 9-amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds |
GB8827704D0 (en) * | 1988-11-28 | 1988-12-29 | Fujisawa Pharmaceutical Co | New acridine derivatives & processes for their production |
US5053513A (en) * | 1990-03-29 | 1991-10-01 | Hoechst-Roussel Pharmaceuticals Incorporated | Method of reducing a carbonyl containing acridine |
-
1992
- 1992-07-30 US US07/921,791 patent/US5247091A/en not_active Expired - Fee Related
-
1993
- 1993-07-19 MX MX9304594A patent/MX9304594A/es not_active IP Right Cessation
- 1993-07-21 TW TW082105784A patent/TW226363B/zh active
- 1993-07-22 EP EP93111751A patent/EP0581194A1/en not_active Withdrawn
- 1993-07-28 FI FI933384A patent/FI933384A/fi unknown
- 1993-07-28 NZ NZ248266A patent/NZ248266A/en unknown
- 1993-07-29 IL IL106530A patent/IL106530A0/xx unknown
- 1993-07-29 HU HU9302214A patent/HUT65497A/hu unknown
- 1993-07-29 JP JP5186544A patent/JPH0820577A/ja active Pending
- 1993-07-29 NO NO932732A patent/NO179581C/no unknown
- 1993-07-29 KR KR1019930014501A patent/KR940005548A/ko not_active Application Discontinuation
- 1993-07-29 CA CA002101568A patent/CA2101568A1/en not_active Abandoned
- 1993-07-29 PL PL93299871A patent/PL299871A1/xx unknown
- 1993-07-29 AU AU44245/93A patent/AU674323B2/en not_active Expired - Fee Related
- 1993-07-29 CN CN93109307A patent/CN1085208A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4631286A (en) * | 1984-10-25 | 1986-12-23 | Hoechst-Roussel Pharmaceuticals Inc. | 9-amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds |
Non-Patent Citations (21)
Title |
---|
A. Osbirk and E. B. Pedersen, Acta Chemica Scandinavica B, vol. 33, published 1979, pp. 313 318, entitled Phosphoramides, X.* Phosphorous Pentaoxide Amine Mixtures and HMPT as Reagents in the Synthesis of 4 Amino and 4 Dimethylamino 2,3 polymethylenequinolines . * |
A. Osbirk and E. B. Pedersen, Acta Chemica Scandinavica B, vol. 33, published 1979, pp. 313-318, entitled "Phosphoramides, X.* Phosphorous Pentaoxide Amine Mixtures and HMPT as Reagents in the Synthesis of 4-Amino- and 4-Dimethylamino-2,3-polymethylenequinolines". |
Acridines, edited by R. M. Acheson, Second Edition, John Wiley & Sons, Inc., published 1973, p. 476. * |
E. T. Michalson, et al., Heterocycles, vol. 30, pp. 415 425, published 1990, entitled Synthesis of 9 (1 Azetidinyl) 1,2,3,4 tetrahydroacridine . * |
E. T. Michalson, et al., Heterocycles, vol. 30, pp. 415-425, published 1990, entitled "Synthesis of 9-(1-Azetidinyl)-1,2,3,4-tetrahydroacridine". |
G. K. Patnaik, et al., Journal of Medicinal Chemistry, vol. 9, pp. 483 to 488, published Jul., 1966, entitled "Compounds Acting on the Central Nervous System, IV. 1-Substituted 2,3-Polymethylenequinolines". |
G. K. Patnaik, et al., Journal of Medicinal Chemistry, vol. 9, pp. 483 to 488, published Jul., 1966, entitled Compounds Acting on the Central Nervous System, IV. 1 Substituted 2,3 Polymethylenequinolines . * |
L. W. Haynes and A. G. Cook in "Enamines--Synthesis, Structure, and Reactions,", 2nd Edition, A. G. Cook, Editor, Marcel Dekker, Inc., New York, N.Y., published 1988, pp. 103 to 114, and Chapter 9. |
L. W. Haynes and A. G. Cook in Enamines Synthesis, Structure, and Reactions, , 2nd Edition, A. G. Cook, Editor, Marcel Dekker, Inc., New York, N.Y., published 1988, pp. 103 to 114, and Chapter 9. * |
P. K. Khandelwal and B. C. Joshi, Defense Science Journal, vol. 21, pp. 199 and 200, published 1971, entitled "Preparation of 2-(N-Morpholinyl)indene and Its Unusual Stability". |
P. K. Khandelwal and B. C. Joshi, Defense Science Journal, vol. 21, pp. 199 and 200, published 1971, entitled Preparation of 2 (N Morpholinyl)indene and Its Unusual Stability . * |
P. W. Hickmott, Tetrahedron, vol. 38, pp. 2005 to 2007, published 1962, entitled "Enamines: Recent Advances in Synthetic, Spectroscopic, Mechanistic, and Stereochemical Aspects-I". |
P. W. Hickmott, Tetrahedron, vol. 38, pp. 2005 to 2007, published 1962, entitled Enamines: Recent Advances in Synthetic, Spectroscopic, Mechanistic, and Stereochemical Aspects I . * |
S. F. Dyke, "The Chemistry of Enamines", Cambridge University Press, London, England, published 1973, pp. 8 and 9. |
S. F. Dyke, The Chemistry of Enamines , Cambridge University Press, London, England, published 1973, pp. 8 and 9. * |
U. Edlund, Acta. Chemica Scandinavica, vol. 26, p. 2972, published 1972, entitled "2-(N-Pyrrolidyl)indene; an Enamine of Unusual Stability". |
U. Edlund, Acta. Chemica Scandinavica, vol. 26, p. 2972, published 1972, entitled 2 (N Pyrrolidyl)indene; an Enamine of Unusual Stability . * |
W. K. Summers, et al., The New England Journal of Medicine, vol. 315, pp. 1241 1245, published Nov. 13, 1986, entitled Oral Tetrahydroaminoacridine in Long Term Treatment of Senile Dementia, Alzheimer Type . * |
W. K. Summers, et al., The New England Journal of Medicine, vol. 315, pp. 1241-1245, published Nov. 13, 1986, entitled "Oral Tetrahydroaminoacridine in Long-Term Treatment of Senile Dementia, Alzheimer Type". |
W. P. Brian and B. L. Souther, Journal of Medicinal Chemistry, vol. 8, pp. 143 to 144, published Jan., 1965, entitled "New Derivatives of 9-Amino-1,2,3,4-tetrahydroacridine". |
W. P. Brian and B. L. Souther, Journal of Medicinal Chemistry, vol. 8, pp. 143 to 144, published Jan., 1965, entitled New Derivatives of 9 Amino 1,2,3,4 tetrahydroacridine . * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994021614A1 (en) * | 1993-03-24 | 1994-09-29 | Merck & Co., Inc. | SUBSTITUTED 3-PHENANTHRIDINONE DERIVATIVES AS 5α-REDUCTASE INHIBITORS |
US5621104A (en) * | 1993-03-24 | 1997-04-15 | Merck & Co., Inc. | Substituted 3-phenanthridinone derivatives as 5-alpha-reductase inhibitors |
WO2012074860A1 (en) | 2010-12-03 | 2012-06-07 | Dow Agrosciences Llc | Processes for the preparation of enamines |
Also Published As
Publication number | Publication date |
---|---|
JPH0820577A (ja) | 1996-01-23 |
NO179581C (no) | 1996-11-06 |
AU674323B2 (en) | 1996-12-19 |
HU9302214D0 (en) | 1993-11-29 |
MX9304594A (es) | 1994-02-28 |
FI933384A0 (fi) | 1993-07-28 |
TW226363B (xx) | 1994-07-11 |
NO932732D0 (no) | 1993-07-29 |
PL299871A1 (en) | 1994-04-05 |
HUT65497A (en) | 1994-06-28 |
IL106530A0 (en) | 1993-11-15 |
NZ248266A (en) | 1997-01-29 |
NO179581B (no) | 1996-07-29 |
NO932732L (no) | 1994-01-31 |
CA2101568A1 (en) | 1994-01-31 |
EP0581194A1 (en) | 1994-02-02 |
CN1085208A (zh) | 1994-04-13 |
FI933384A (fi) | 1994-01-31 |
AU4424593A (en) | 1994-02-03 |
KR940005548A (ko) | 1994-03-21 |
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